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帕金森病中的多巴胺 D-1 受体与环磷酸腺苷依赖性磷酸化

Dopamine D-1 receptor and cyclic AMP-dependent phosphorylation in Parkinson's disease.

作者信息

Cash R, Raisman R, Ploska A, Agid Y

出版信息

J Neurochem. 1987 Oct;49(4):1075-83. doi: 10.1111/j.1471-4159.1987.tb09996.x.

DOI:10.1111/j.1471-4159.1987.tb09996.x
PMID:2887632
Abstract

D-1 and D-2 receptor densities, evaluated respectively by [3H]SCH 23390 and [3H]spiperone binding, and DARPP-32 (dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein-32K) concentrations, were studied in the brains of control and parkinsonian subjects postmortem. D-2 receptor density was unchanged in the putamen of parkinsonian patients. D-1 receptor density was unchanged in the putamen and substantia nigra pars reticulata (SNR) of parkinsonian patients, but decreased by 28% in the substantia nigra pars compacta (SNC). DARPP-32, which is localized in the same structures as D-1 receptors of which it is thought to represent the intracellular messenger, decreased by 45% in the putamen, 66% in the SNR, and 79% in the SNC. The decrease in D-1 receptors in the SNC may be due to degeneration of pallidonigral GABAergic neurons, but some of the D-1 receptors may be on the nigrostriatal dopaminergic neurons themselves. The dissociation between the alteration of D-1 receptor densities and DARPP-32 concentrations in both the striatum and substantia nigra, which are of the same order in the two structures, may be an index of functional hypoactivity of D-1 neurotransmission.

摘要

通过[3H]SCH 23390和[3H]螺哌隆结合分别评估的D-1和D-2受体密度,以及多巴胺和3':5'-单磷酸腺苷调节的磷蛋白-32K(DARPP-32)浓度,在对照和帕金森病患者死后的大脑中进行了研究。帕金森病患者壳核中的D-2受体密度未发生变化。帕金森病患者壳核和黑质网状部(SNR)中的D-1受体密度未发生变化,但黑质致密部(SNC)中的D-1受体密度下降了28%。DARPP-32与D-1受体定位于相同结构,被认为是D-1受体的细胞内信使,其在壳核中下降了45%,在SNR中下降了66%,在SNC中下降了79%。SNC中D-1受体的减少可能是由于苍白球黑质γ-氨基丁酸能神经元的变性,但一些D-1受体可能位于黑质纹状体多巴胺能神经元自身上。纹状体和黑质中D-1受体密度变化与DARPP-32浓度变化之间的分离,在这两个结构中变化程度相同,可能是D-1神经传递功能减退的一个指标。

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